19 Sept 2020; Updated 25 Nov 2020
1. Why Is High Frequency Rapid Testing a Prevention Strategy?
There are communities throughout the US with COVID19 infection rates that are neither at zero nor at elevated levels. These communities are moving in the right direction, with the probability of an infection appearing within an elementary school community is relatively low for some areas. Yet, the lack of data means elementary schools in these communities are still flying blind. So, how can rapid testing stop transmission chains in schools and how can it be done with a high level of transparency? It starts with mapping out reactive and proactive testing.
Symptomatic testing is reactive. By the time a symptomatic individual gets tested and receives results, their SARS-CoV-2 infectiousness period has already been underway and peaked [15-16]. In the context of facilities such as nursing homes or schools, this translates into outbreaks.
When testing proactively (e.g., rapid testing), the goal is to test, capture and isolate those infections in the early stages of infectiousness but not showing symptoms or with obvious exposures (e.g., pre-symptomatic and asymptomatic infections)[2-3]. This has been demonstrated to shift disease dynamics when administered daily or even every 3 days . In other words, rapid testing is not just about individual treatment and isolation. It translates into infections averted, which drives down the reproductive rate of infection within a community.
In this respect, testing acts as prevention. But, even in communities with elevated infection rates, blanket testing is not the answer. Mapping out for whom and when testing occurs is key to preventing outbreaks.
2. Rapid Testing Strategy: When & Who
In an elementary school setting, there are three potential time points when students & school staff should be universally tested: 1) at re-entry, 2) when exposed to a COVID positive individual and/or 3) when symptomatic. But, on an ongoing basis, the evidence indicates a need to prioritize school staff for ongoing rapid test screening.
While there is little doubt younger school children can acquire and transmit, they do not transmit efficiently [7-9] (see here for detailed COVID-19 evidence related to children and transmission). In scenarios where younger children have transmitted, they have reflected large scale, high intensity outbreaks [10-11]. In contrast, adults & older school children have been explicitly implicated as sources in big & small outbreaks and in school settings [12-14]. Based on a 25 million+ COVID case-load globally, transmission patterns suggest the focus for rapid testing should remain strategically on those groups who have been shown to consistently act as the index cases (e.g., sources) of large and small outbreaks: adults.
This translates into a school testing strategy with 4 distinct parts, including:
i) Universal re-entry testing for all those physically on school grounds for all
ii) Ongoing universal symptomatic screening on school grounds for all
iii) Ongoing universal symptomatic testing active referrals to off campus community-based testing resources for all and;
iv) Ongoing school-based rapid COVID-19 testing for school staff.
3. What is the Direct Evidence to Support High Frequency Rapid Test Strategies?
Nursing homes and hospitals have been the site of concentrated COVID-19 prevention and response efforts in US. Two large scale, robust studies offer important insight into rapid testing.
A multi-site study demonstrated those nursing homes with multiple test points (12/26 facilities) saw a decrease from 35 to 18% of lab confirmed SARS-CoV-2 infections . Rapid testing led to earlier isolation and in turn, the ability to break transmission chains. A second study among 288 nursing homes quantified the compounding effect of rapid testing delays. For each day between the first (e.g., index) case and completion of facility-wide rapid testing, 1.3 additional cases were identified .
In hospital settings, early pandemic shortages required limiting patients and staff to symptomatic testing. As tests became available, universal testing was instituted. The different forms of testing provided important insight via retrospective analysis. Universal testing was able to highlight key differences in how infections were spreading between staff versus patients. Furthermore, universal testing also provided the direct data to identify asymptomatic infection patterns that went undetected during symptomatic testing .
In each of these settings, as well as multiple university-run rapid testing pilots in the US, the efficiency to capture infections rests on the high frequency at which tests were administered (1-2 days). Two additional modeling studies further confirm high frequency tests (~1-3 days). One of which identified rapid screening every 2 days among a hypothetical 5,000 person college cohort, with 10 seeded asymptomatic infections, enabled containment of the virus . A second modeling study identified daily or every 3 days as providing efficient frequency to quickly isolate new infections before secondary infections could occur  (See below).
4. What About the Criticisms of Rapid Testing?
A major criticism of rapid tests is that they have lower sensitivity (e.g., more false negatives) compared to RT-PCR tests. However, it has also been established in SARS-CoV-2 research that conducting a high frequency of rapid testing can outweigh the need to maximize sensitivity of tests for screening purposes [1-3]. Specifically, when administered daily or every 3 days, the less sensitive tests have been able to efficiently capture infections . In contrast, the damage from delays in timeline to RT-PCR tests delays have repeatedly contributed to outbreaks.
How can this be? Much of this has to do with optimizing test timing between a person acquiring a SARS-CoV-2 infection and before they pass it to others. And in the case of SARS-CoV-2, that timeline-- reflecting an infectiousness period -- starts before symptom onset [2-3, 15-16, 18].
Studies consistently identify median infectiousness (~2-5 days before symptom onset) and peaking just before and at symptom onset (1 day before or at symptom onset) [15,17-18]. However, ranges have been relatively wide. For instance, a well-documented sample of 77 infector-infectee pairs, identified cases of transmission 12.3 days before symptom onset but found transmission peaks remained consistent with other studies-- at symptom onset (95% CI: 5.9-17.0) . Thus, ongoing high frequency rapid testing in a community means that —as soon as a positive test arises, transmission to others has a minimal amount of time to occur.
Furthermore, the ability of rapid tests to capture infections relates to the probability a person in a community has COVID-19 (e.g., pre-test probability). As mapped out by Sax, in a population of 1000 asymptomatic individuals with a 1% pre-test probability (e.g., positive test rate), the odds of a missed infection when using a test with 80% sensitivity is ~ 2/1000 .
A second criticism of rapid testing is the potential for interpretation errors in reading results given the wider range of health professionals who would be administering and reading rapid tests . And while the potential for interpretation errors clearly exists, the answer to this concern in a pandemic is training. Read expert opinions about this specific COVID-19 rapid test here.
Finally, another argument against rapid tests is that transmission prior to symptoms may occur too infrequently and in turn, not enough of a problem to warrant ongoing rapid testing. But, adults who have asymptomatic/ pre-symptomatic infections are most likely to be an index case in a transmission chain, and these are not rare infections [16, 22-26].
One high quality study identified pre-symptomatic transmission accounting for 44% of infections among 77 infector-infectee pairs , while estimates of asymptomatic infections have ranged from 9% to >50% [22-26]. The large variations is likely attributed to misclassification of symptoms . However, tracing asymptomatic infections in more closed settings reveals valuable insight to this problem.
In hospital settings, two diverse in-patient populations in NYC (e.g., obstetrics and psychiatric in-patients), reported similar rates of asymptomatic individuals (~13%) during the same time period . In another closed setting, a February 2020 analysis cruise ship outbreak estimated asymptomatic infections to be the source of 69% (20-85%) of all infections among 3,700 individuals . Interestingly, a novel machine learning approach modeled asymptomatic cases based on real world data from China. This model suggests a possible 35% of infections detected, while 65% were asymptomatic and remained undetected .
Whether it is a matter of extremely mild symptoms that go unnoticed or true asymptomatic cases, these cases are key to controlling transmission in school settings .
5. Practical Translations of the Evidence: Coordination, Triggers to Action & Building Community Trust in an Untrusted System
A. Coordination : How Does School-based Rapid Testing Link to Other Types of Testing?
There are three types of COVID-19 testing, each with a distinct objective.
Symptomatic testing: Testing for individuals showing active signs/symptoms of SARS-CoV-2 or who had a specific exposure to a COVID positive individual. The relevant (e.g., diagnostic) test strategy is a specific molecular test via RT-PCR to detect active virus with high sensitivity and high specificity (e.g., less false positives & less false negatives).
Screening (rapid) testing: Testing to identify individuals with COVID-19 infections regardless of symptom or exposure status. The purpose of screening tests within a school community is to capture pre-symptomatic or asymptomatic COVID-19 cases with the explicit goal of stopping transmission lines within the community (e.g., avoid an outbreak). The appropriate tests for these purposes are rapid (e.g., antigen) tests, which are less sensitive but more frequent testing can compensate for the lack of test sensitivity [1,3].
Surveillance testing: Large-scale community wide testing to understand how the infection is spreading within multiple community settings. Examples of surveillance testing would be using pooled testing in low prevalence areas to identify asymptomatic cases, but where individual results are not provided. Thus, this type of testing can inform wider decision-making but cannot inform individual COVID-19 status. The types of tests used for surveillance are antibody tests or pooled testing.
In low COVID-19 prevalence communities or where resources are constrained, alternative strategies such as pooled testing or even wastewater COVID-19 testing have demonstrated feasible and efficient infection detection strategies [5-6].
In contrast, school contexts in communities with moderate to high COVID-19 rates need a more direct approach. Utilizing the first two testing strategies are key to reduce transmission within a school community.
B. Triggers to Action: Elementary School Settings
Specifics of testing protocols depend largely on the sensitivity & specificity of available rapid tests, the frequency at which tests are administered, age of students and community infection rates. However, there are general guiding principles and evidence-based recommendations that can be used as a springboard for more localized planning. Below is a snapshot of triggers to action in a hypothetical elementary school setting.
A. Re-entry testing: Establishing a baseline. Universal testing of staff and students for those planning to be physically on campus. Testing done prior to arrival on campus via RT-PCR requires a short window between testing, results, and being on campus (e.g., ~1- 2 days) [1-3, 10].
B. Symptomatic testing: Ongoing links to community testing off school grounds. Any school community member who has any signs/symptoms should not be coming onto school grounds. These cases should be referred to community testing resources for RT-PCR tests.
School Triggers to Action:
• If a COVID RT-PCR test is positive, immediate isolation of the individual and household members, along with reporting to county resources to initiate contact tracing protocols.
• If a COVID RT-PCR testing is negative but the individual is symptomatic, the American Pediatric Association recommends isolation from the school setting until symptoms resolve . This is applicable to both children and adults.
C. Pre-symptomatic/ asymptomatic rapid testing: Ongoing screening for school staff. High frequency (every 1 to 3 days) rapid (e.g., antigen) tests, with immediate results (e.g., 15 minutes) [1-3].
School Triggers to Action:
• A positive rapid test: The individual moves into isolation for 10-14 days from the school setting & reporting done to the county liaison for contact tracing.
• A negative rapid test result but the individual had a known direct exposure: The negative test should be considered a ‘presumptive negative’ test. In other words, the negative test should be considered in conjunction with clinical and exposure history, as per FDA guidance as of 8/14/20. The individual should be referred off campus for a more rigorous RT-PCR test.
• A negative rapid test result but the individual has flu-like symptoms: In settings where there is moderate to high community spread, any COVID-19 symptoms that may mimic flu should receive an RT-PCR COVID-19 test.
C. Building Community Trust in a Pandemic & Moving Forward
School administrators & educators are faced with enormous pressure to act without the resources or full picture of evidence-based guidance to reduce risks of COVID-19 outbreaks. At the same time, the cascading effects for children, particularly young school children, grow exponentially.
If rapid test protocols maintain a high level of transparency-- where high quality evidence is the basis of decision-making-- it can provide tangible assurance to educators and parents in an untrusted system.
1. Larremore, D. B., Wilder, B., Lester, E., Shehata, S., Burke, J. M., Hay, J. A., ... & Parker, R. (2020). Test sensitivity is secondary to frequency and turnaround time for COVID-19 surveillance. MedRxiv.
2. Hatfield, K. M., Reddy, S. C., Forsberg, K., Korhonen, L., Garner, K., Gulley, T., ... & Sievers, M. (2020). Facility-wide testing for SARS-CoV-2 in nursing homes—seven US jurisdictions, March–June 2020. Morbidity and Mortality Weekly Report, 69(32), 1095.
3. Sanchez, G. V., Biedron, C., Fink, L. R., Hatfield, K. M., Polistico, J. M. F., Meyer, M. P., ... & Kiama, K. (2020). Initial and repeated point prevalence surveys to inform SARS-CoV-2 infection prevention in 26 skilled nursing facilities—Detroit, Michigan, March–May 2020.
4. K. Ketchum. Modern Health Care. Would Abott's Antigen Test Solve COVID-19 Testing Problems? Stakeholders Emphasize Caution. 1 Sept 2020. Read expert opinions about this specific COVID-19 rapid test here.
5. Peccia, J., Zulli, A., Brackney, D.E. et al. Measurement of SARS-CoV-2 RNA in wastewater tracks community infection dynamics. Nat Biotechnol (2020). https://doi.org/10.1038/s41587-020-0684-z
6. Garg, J., Singh, V., Pandey, P., Verma, A., Sen, M., Das, A., & Agarwal, J. Evaluation of sample pooling for diagnosis of COVID‐19 by Real time PCR‐A resource saving combat strategy. Journal of Medical Virology.
7. Stringhini, S., Wisniak, A., Piumatti, G., Azman, A. S., Lauer, S. A., Baysson, H., ... & Yerly, S. (2020). Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study. The Lancet. Children don’t transmit efficiently
8. Kim, J., Choe, Y. J., Lee, J., Park, Y. J., Park, O., Han, M. S., ... & Choi, E. H. (2020). Role of children in household transmission of COVID-19. Archives of Disease in Childhood.
9. Highfield. R. Coronavirus: Hunting Down COVID-19. Interview with Kari Stefansson. Science Museum Group. 27 April 2020.
10. Szablewski, C. M. (2020). SARS-CoV-2 Transmission and Infection Among Attendees of an Overnight Camp—Georgia, June 2020. MMWR. Morbidity and mortality weekly report, 69.
11. Lopez, A. S. (2020). Transmission Dynamics of COVID-19 Outbreaks Associated with Child Care Facilities—Salt Lake City, Utah, April–July 2020. MMWR. Morbidity and Mortality Weekly Report, 69.
12. Macartney, K., Quinn, H. E., Pillsbury, A. J., Koirala, A., Deng, L., Winkler, N., ... & Brogan, D. (2020). Transmission of SARS-CoV-2 in Australian educational settings: a prospective cohort study. The Lancet Child & Adolescent Health.
13. Guthrie, B., Tordoff, D., Meisner, J., Tolentino, L., Jian, W., …..Ross, J. (2020). Summary of School Re-Opening Models and Implementation Approaches During the COVID-19 Pandemic. Washing State Dept of Health & Univ Washington.
14. Fontanet, A., Tondeur, L., Madec, Y., Grant, R., Besombes, C., Jolly, N., ... & Temmam, S. (2020). Cluster of COVID-19 in northern France: A retrospective closed cohort study. medRxiv.
15. Zhang, Y., Muscatello, D., Tian, Y., Chen, Y., Li, S., Duan, W., ... & Yang, P. (2020). Role of presymptomatic transmission of COVID-19: evidence from Beijing, China. J Epidemiol Community Health.
16. He, X., Lau, E. H., Wu, P., Deng, X., Wang, J., Hao, X., ... & Mo, X. (2020). Temporal dynamics in viral shedding and transmissibility of COVID-19. Nature medicine, 26(5), 672-675.
17. Expert Taskforce for the COVID-19 Cruise Ship Outbreak, Epidemiology of COVID-19 Outbreak on Cruise Ship Quarantined at Yokohama, Japan, February 2020. Emerging infectious diseases, 26(11).
18. Lau, E. H., & Leung, G. M. (2020). Reply to: Is presymptomatic spread a major contributor to COVID-19 transmission?. Nature Medicine, 1-2.
19. Paltiel, A. D., Zheng, A., & Walensky, R. P. (2020). Assessment of SARS-CoV-2 screening strategies to permit the safe reopening of college campuses in the United States. JAMA network open, 3(7), e2016818-e2016818.
20. Sax, P. Relieving the COVID19 Testing Logjam. New England Journal of Medicine Journal Watch.
21. Zhang, E., LeQuesne, E., Fichtel, K., Ginsberg, D., & Frankle, W. G. (2020). In-patient psychiatry management of COVID-19: Rates of asymptomatic infection and on-unit transmission. BJPsych Open, 6(5).
22. Nishiura, H., Kobayashi, T., Miyama, T., Suzuki, A., Jung, S. M., Hayashi, K., ... & Linton, N. M. (2020). Estimation of the asymptomatic ratio of novel coronavirus infections (COVID-19). International journal of infectious diseases, 94, 154.
23. Mizumoto, K., Kagaya, K., Zarebski, A., & Chowell, G. (2020). Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020. Eurosurveillance, 25(10), 2000180.
24. Kronbichler, A., Kresse, D., Yoon, S., Lee, K. H., Effenberger, M., & Shin, J. I. (2020). Asymptomatic patients as a source of COVID-19 infections: A systematic review and meta-analysis. International Journal of Infectious Diseases, 98, 180-186.
25. Expert Taskforce for the COVID-19 Cruise Ship Outbreak, Epidemiology of COVID-19 Outbreak on Cruise Ship Quarantined at Yokohama, Japan, February 2020. Emerging infectious diseases, 26(11).
26. Lucey, M., Macori, G., Mullane, N., Sutton-Fitzpatrick, U., Gonzalez, G., Coughlan, S., ... & Schaffer, K. Whole-Genome Sequencing Confirms SARS-CoV-2 Transmission between Healthcare Workers and Patients.
27. Meyerowitz, E., Richterman, A., Bogoch, I., Low, N., & Cevik, M. (2020). Towards an Accurate and Systematic Characterization of Persistently Asymptomatic Infection with SARS-CoV-2. Available at SSRN 3670755.
28. Emery, J. C., Russell, T. W., Liu, Y., Hellewell, J., Pearson, C. A., Knight, G. M., ... & Houben, R. M. (2020). The contribution of asymptomatic SARS-CoV-2 infections to transmission on the Diamond Princess cruise ship. eLife, 9, e58699.
29. Yu, Y., Liu, Y. R., Luo, F. M., Tu, W. W., Zhan, D. C., Yu, G., & Zhou, Z. H. (2020). COVID-19 Asymptomatic Infection Estimation. medRxiv. [23 April 2020].
30. Furuse, Y. et al. Clusters of coronavirus disease in communities, Japan, January–April 2020. Emerg. Infect. Dis. https://doi.org/10.3201/eid2609.202272 (2020).
31. Hellewell, J., Abbott, S., Gimma, A., Bosse, N. I., Jarvis, C. I., Russell, T. W., ... & Flasche, S. (2020). Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts. The Lancet Global Health.
32. American Pediatric Association. Planning Considerations: Guidance for School Re-entry.
33. COVID-19 in children and the role of school settings in COVID-19 transmission, 6 August 2020. Stockholm: ECDC; 2020.